目的探讨脓毒症大鼠心肌组织内毒素信号转导复合受体.Toll样受体4(TLR4)/髓样分化蛋白.2(MD2)基因表达的变化情况。研究其与心肌组织肿瘤坏死因子-α(TNF-α)基因表达的关系。方法采用腹腔注射5mg/kg体重内毒素(LPS)制作大鼠脓毒症模型。动物分为正常对照组(10只),内毒素注射后1、2、6h组(各10只),利用逆转录-聚合酶链反应(RT-PCR)方法检测心肌组织TLR4/MD2以及TNF-α的基因表达。结果LPS注射后1h,TLR4/MD-2及TNF-α基因表达开始升高,2h达高峰,6h逐渐下降,各时间点的表达均显著高于对照组(P〈0.01)。相关分析表明,心肌TUM/MD2基因表达分别与TNF-α基因表达呈显著正相关(P〈0.05)。结论LPS可上调心肌组织TLR4/MD-2基因表达并诱导早期炎症细胞因子TNF-α基因表达。TLR4识别LPS信号是以TLR4/MD-2复合受体的形式完成的。而且在识别过程中,MD-2是TLR4必需的作用分子。
Objective To investigate the change of Toll-like receptor 4 (TLR4) and myeloid differential protein-2 (MD-2) gene expression in myocardium in septic rats and evaluate the relationship of the gene expression between TLR4/MD-2 and TNF-α. Methods Sepsis was replicated by intraperitonesl injection of LPS (5 mg/kg). Forty Wistar rats were randomly divided into normal controls (n = 10), LPS 1 h, 2 h, 6 h groups ( n = 10, respectively). Rats were sacrificed at different time points. The gene expression of tissue TLR4/MD-2 and TNF-α in myocardium was measured by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Results TLR4/MD-2 mRNA and TNF-α mRNA could be detected in myocardium with very low values in normal controls, but they were markedly up-regulated and peaked at 2 h, and down-regulated at 6 h. The expression of TLR4/MD-2 mRNA had a positive correlation with TNF-α mRNA in myocardium. Conclusion LPS could up-regulate the expression of TLR4/MD-2 mRNA in myocardium. TLR4 recognizes LPS by the coreceptor-TLR4/MD-2 complex, and MD-2 is a key regulatory molecule in sepsis.